Journal Article

miR-34a/DRP-1-mediated mitophagy participated in cisplatin-induced ototoxicity via increasing oxidative stress

Huang, Lingfei, Wang, Haiyan, Kang, Weibiao, He, Feinan, Tang, Yiyang, Yang, Haidi, Huang, Xiaotong, Jia, Haiying, Lin, Hanqing, Gong, Sisi, Ye, Yongyi, Zhang, Tao

2023

Overview

Purpose Cisplatin is a widely used and effective chemotherapeutic agent for most solid malignant tumors. However, cisplatin-induced ototoxicity is a common adverse effect that limits the therapeutic efficacy of tumors in the clinic. To date, the specific mechanism of ototoxicity has not been fully elucidated, and the management of cisplatin-induced ototoxicity is also an urgent challenge. Recently, some authors believed that miR34a and mitophagy played a role in age-related and drug-induced hearing loss. Our study aimed to explore the involvement of miR-34a/DRP-1-mediated mitophagy in cisplatin-induced ototoxicity. Methods In this study, C57BL/6 mice and HEI-OC1 cells were treated with cisplatin. MiR-34a and DRP-1 levels were analyzed by qRT‒PCR and western blotting, and mitochondrial function was assessed via oxidative stress, JC-1 and ATP content. Subsequently, we detected DRP-1 levels and observed mitochondrial function by modulating miR-34a expression in HEI-OC1 cells to determine the effect of miR-34a on DRP-1-mediated mitophagy. Results MiR-34a expression increased and DRP-1 levels decreased in C57BL/6 mice and HEI-OC1 cells treated with cisplatin, and mitochondrial dysfunction was involved in this process. Furthermore, the miR-34a mimic decreased DRP-1 expression, enhanced cisplatin-induced ototoxicity and aggravated mitochondrial dysfunction. We further verified that the miR-34a inhibitor increased DRP-1 expression, partially protected against cisplatin-induced ototoxicity and improved mitochondrial function. Conclusion MiR-34a/DRP-1-mediated mitophagy was related to cisplatin-induced ototoxicity and might be a novel target for investigating the treatment and protection of cisplatin-induced ototoxicity.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Age / Analysis / Animals / Antimitotic agents / Antineoplastic agents / Apoptosis / Autophagy / Biomedical and Life Sciences / Biomedicine / Cancer / Chemotherapy / Cisplatin / Cisplatin - toxicity / DRP-1 / Dynamins - genetics / Hair / Health aspects / Hearing loss / Laboratory animals / Mice / Mice, Inbred C57BL / MicroRNAs / MicroRNAs - genetics / miR-34a / Mitochondria / Mitophagy / Ototoxicity / Ototoxicity - genetics / Oxidative Stress / Pathogenesis / Pharmacology/Toxicology / Protein expression / Proteins / Tumors / Western blotting